Metabolic profiling of marine sponges as a tool to discover novel natural products

Abstract

In this project metabolic profiling was explored as a means for finding unique and novel natural products. Natural products have had a vital role in drug discovery throughout history and in recent times, that includes the world oceans more and more. Therefore two related species of marine sponges, where the samples were collected from different locations, was chosen to test the methodology. This project was performed at MabCent, a research center which focuses on bioactive compounds from Arctic and sub-Arctic organisms. A high-resolution mass spectrometer (HR-MS) was used to provide data for the analysis and a processing software program was used for interpretation of the data. The sponge`s metabolic profiles clearly grouped according to species. A known bioactive compound, barettin, was present in all the samples although in different amounts. One of the species contained a unique compound that was not present in the samples from the other species. The compound now labeled MBC-169 had an m/z: 400 and an elemental composition of C21H37NO4S, which was determined by the MS software. MBC-169 was isolated with the help of preparative high performance liquid chromatography (HPLC) before the structure was determined with the combination of HR-MS and nuclear magnetic resonance (NMR) data. After the structure elucidation MBC-169 was tested for antioxidant activity in two different assays as well as antibiotic activity, and for kinase inhibiting properties. In addition this thesis provides background information of challenges when natural products are used as a source for discovering novel bioactive compounds and how those challenges were overcome in this particular project.